The prefrontal cortex (PFC) is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas. The prefrontal cortex plays a critical role in higher cognitive function. Dysregulation of prefrontal cortex-dependent cognition is associated with a variety of disorders and conditions, including Attention Deficit/Hyperactivity Disorder (ADHD) and normal aging.
There are limited pharmacological treatments available that improve prefrontal cortex-dependent cognition. Psychostimulants, such as methylphenidate (MPH; Ritalin®) and amphetamine, are the most effective and widely used class of drugs for the treatment of ADHD. The therapeutic effects of these drugs are strongly linked to their ability to improve cognitive processes dependent on the prefrontal cortex (Greenhill, 2001, Stimulant Drugs and ADHD: Basic and Clinical Neuroscience, Oxford University Press, New York).
The ability of MPH and other psychostimulants to enhance PFC-dependent cognition is observed in both normal and ADHD-affected individuals. However, despite their effectiveness in treating ADHD, there are a number of potential serious risks and potential adverse actions associated with the use of stimulants, including abuse. Given these risks, there is tremendous interest in developing non-psychostimulant drugs for use in the treatment of ADHD and other disorders or conditions associated with impairment in PFC-dependent cognition. In particular, there is a need for non-stimulant drugs that improve PFC-dependent cognition.
Currently, the degree to which a chemical compound improves prefrontal cortex-dependent cognition is assessed by administering the compound to animal or human test subjects and measuring performance in standard behavioral tests of PFC-dependent cognition, such as working memory (Arnsten and Li, 2005, Biol. Psychiatry 57: 1377-1384). This is a labor-intensive procedure that requires extensive training and expertise. It would be advantageous to provide faster methods of assessing the potential facilitatory actions of a compound on PFC-dependent cognition. The present invention provides this and related needs.